Kadi Linda, Selvaraju Ram, de Lys Patricia, Proudfoot Amanda E I, Wells Timothy N C, Boschert Ursula
Department of Immunology, Serono Pharmaceutical Research Institute 14, Chemin des Aulx, 1228 Plan les Ouates, Geneva, Switzerland.
J Neuroimmunol. 2006 May;174(1-2):133-46. doi: 10.1016/j.jneuroim.2006.01.011. Epub 2006 Mar 30.
Chemokines have recently been postulated to have important functions in the central nervous system (CNS) in addition to their principal role of directional migration of leukocytes. In particular, it has been shown that chemokines may play a role in the regulation of oligodendrocyte biology. Here, we have chosen to study the role of certain chemokines in regulating myelination. We have used the murine oligodendrocyte precursor-like cell line, Oli-neu, and primary mixed cortical cultures as experimental systems to assess their activities on oligodendrocyte precursor proliferation and developmental in vitro myelination. GRO-alpha, IL-8, SDF-1alpha and RANTES dose-dependently increased proliferation of this mouse A2B5 precursor-like cell line, while MCP-1 did not. Furthermore, the CXC chemokines GRO-alpha, IL-8 and SDF-1alpha stimulated myelin basic protein synthesis in a dose-dependent manner in primary myelinating cultures and enhanced myelin segment formation in this system, while the CC chemokines MCP-1 and RANTES did not. We also demonstrate that the receptor for SDF-1alpha, CXCR4, is expressed in mixed cortical cultures by PDGFalphaR positive oligodendrocyte precursors (OLPs) as well as by Oli-neu cells. SDF-1alpha induced proliferation in primary mixed cultures and the Oli-neu cell line was mediated through this receptor. We propose, therefore, that CXC chemokines and in particular SDF-1alpha regulates CNS myelination via their effects on cells of the oligodendrocyte lineage, specifically stimulation of OLP proliferation.
最近有研究推测，趋化因子除了在白细胞定向迁移中发挥主要作用外，在中枢神经系统（CNS）中也具有重要功能。特别是，已有研究表明趋化因子可能在少突胶质细胞生物学调节中发挥作用。在此，我们选择研究某些趋化因子在调节髓鞘形成中的作用。我们使用小鼠少突胶质前体细胞样细胞系Oli-neu和原代混合皮质培养物作为实验系统，以评估它们对少突胶质前体细胞增殖和体外发育性髓鞘形成的影响。GRO-α、IL-8、SDF-1α 和 RANTES 呈剂量依赖性地增加了这种小鼠 A2B5 前体细胞样细胞系的增殖，而 MCP-1 则没有。此外，CXC 趋化因子 GRO-α、IL-8 和 SDF-1α 在原代髓鞘形成培养物中以剂量依赖性方式刺激髓鞘碱性蛋白合成，并增强了该系统中的髓鞘节段形成，而 CC 趋化因子 MCP-1 和 RANTES 则没有。我们还证明，SDF-1α 的受体 CXCR4 在混合皮质培养物中由血小板衍生生长因子α受体（PDGFαR）阳性的少突胶质前体细胞（OLP）以及 Oli-neu细胞表达。SDF-1α 在原代混合培养物中诱导增殖，并且 Oli-neu 细胞系中的增殖是通过该受体介导的。因此，我们提出，CXC 趋化因子，特别是 SDF-1α，通过对少突胶质细胞谱系细胞的作用，特别是刺激 OLP 增殖，来调节中枢神经系统的髓鞘形成。
